Role of Cbfa1 in osteoblast differentiation and function

2000 ◽  
Vol 11 (5) ◽  
pp. 343-346 ◽  
Author(s):  
Gerard Karsenty
2007 ◽  
Vol 18 (7) ◽  
pp. 2411-2418 ◽  
Author(s):  
Atsuko Shimoyama ◽  
Masahiro Wada ◽  
Fumiyo Ikeda ◽  
Kenji Hata ◽  
Takuma Matsubara ◽  
...  

Genetic and cell biological studies have indicated that Indian hedgehog (Ihh) plays an important role in bone development and osteoblast differentiation. However, the molecular mechanism by which Ihh regulates osteoblast differentiation is complex and remains to be fully elucidated. In this study, we investigated the role of Ihh signaling in osteoblast differentiation using mesenchymal cells and primary osteoblasts. We observed that Ihh stimulated alkaline phosphatase (ALP) activity, osteocalcin expression, and calcification. Overexpression of Gli2- but not Gli3-induced ALP, osteocalcin expression, and calcification of these cells. In contrast, dominant-negative Gli2 markedly inhibited Ihh-dependent osteoblast differentiation. Ihh treatment or Gli2 overexpression also up-regulated the expression of Runx2, an essential transcription factor for osteoblastogenesis, and enhanced the transcriptional activity and osteogenic action of Runx2. Coimmunoprecipitation analysis demonstrated a physical interaction between Gli2 and Runx2. Moreover, Ihh or Gli2 overexpression failed to increase ALP activity in Runx2-deficient mesenchymal cells. Collectively, these results suggest that Ihh regulates osteoblast differentiation of mesenchymal cells through up-regulation of the expression and function of Runx2 by Gli2.


2020 ◽  
Author(s):  
Samir M. Abdelmagid ◽  
Allison Zajac ◽  
Imad Salhab ◽  
Hyun-Duck Nah

ABSTRACTSeveral reports emphasized the importance of inorganic pyrophosphate (PPi) in hindering osteoblast differentiation and bone matrix mineralization. Its ubiquitous presence is thought to prevent “soft” tissue calcification, whereas its degradation to Pi in bones and teeth by alkaline phosphatase (ALP) may facilitate crystal growth. While the inhibiting role of PPi on osteoblast differentiation and function is largely understood, less is known about its effects on osteoclast determination and activity. In this study, we investigated the role of PPi in bone resorption using calverial organ cultures ex vivo. We present an evidence that PPi stimulated calvarial bone resorption marked by calcium (Ca2+) release in the condition media (CM). We then examined PPi effects on osteoclast differentiation using mouse bone marrow-derived monocytes (BMMs). Our results revealed that PPi enhanced osteoclast differentiation ex vivo, marked by increased number and size of TRAP-stained mature osteoclasts. Moreover, PPi stimulated osteoclastogenesis in BMMs co-cultured with osteoblasts. These data supported the increased osteoclast activity in bone resorption using functional osteo-assays. The finding of PU.1-Egr-1 dependent up-regulation of c-FMS and RANK receptors in BMMs supported the enhanced pre-osteoclast commitment and differentiation. Moreover, osteoclast survival was enhanced by activation of MITF-BCL-2 pathway that was mediated by MAPK-ERK1/2 signaling. Last, our data showed that PPi up-regulated ANK; PPi transporter, during osteoclast differentiation through ERK1/2 phosphorylation whereas mutation of ANK inhibited osteoclastogenesis. Collectively, our data suggest that PPi promotes osteoclast differentiation, survival, and function through PU.1 up-regulation and MITF phosphorylation whereas ANK loss-of-function inhibited osteoclastogenesis.


2017 ◽  
Vol 6 (3) ◽  
pp. 23 ◽  
Author(s):  
Hirohiko Okamura ◽  
Kaya Yoshida ◽  
Hiroyuki Morimoto ◽  
Jumpei Teramachi ◽  
Kazuhiko Ochiai ◽  
...  

Author(s):  
Grace C.H. Yang

The size and organization of collagen fibrils in the extracellular matrix is an important determinant of tissue structure and function. The synthesis and deposition of collagen involves multiple steps which begin within the cell and continue in the extracellular space. High-voltage electron microscopic studies of the chick embryo cornea and tendon suggested that the extracellular space is compartmentalized by the fibroblasts for the regulation of collagen fibril, bundle, and tissue specific macroaggregate formation. The purpose of this study is to gather direct evidence regarding the association of the fibroblast cell surface with newly formed collagen fibrils, and to define the role of the fibroblast in the control and the precise positioning of collagen fibrils, bundles, and macroaggregates during chick tendon development.


Author(s):  
Edna S. Kaneshiro

It is currently believed that ciliary beating results from microtubule sliding which is restricted in regions to cause bending. Cilia beat can be modified to bring about changes in beat frequency, cessation of beat and reversal in beat direction. In ciliated protozoans these modifications which determine swimming behavior have been shown to be related to intracellular (intraciliary) Ca2+ concentrations. The Ca2+ levels are in turn governed by the surface ciliary membrane which exhibits increased Ca2+ conductance (permeability) in response to depolarization. Mutants with altered behaviors have been isolated. Pawn mutants fail to exhibit reversal of the effective stroke of ciliary beat and therefore cannot swim backward. They lack the increased inward Ca2+ current in response to depolarizing stimuli. Both normal and pawn Paramecium made leaky to Ca2+ by Triton extrac¬tion of the surface membrane exhibit backward swimming only in reactivating solutions containing greater than IO-6 M Ca2+ Thus in pawns the ciliary reversal mechanism itself is left operational and only the control mechanism at the membrane is affected. The topographic location of voltage-dependent Ca2+ channels has been identified as a component of the ciliary mem¬brane since the inward Ca2+ conductance response is eliminated by deciliation and the return of the response occurs during cilia regeneration. Since the ciliary membrane has been impli¬cated in the control of Ca2+ levels in the cilium and therefore is the site of at least one kind of control of microtubule sliding, we have focused our attention on understanding the structure and function of the membrane.


2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.


1999 ◽  
Vol 81 (06) ◽  
pp. 951-956 ◽  
Author(s):  
J. Corral ◽  
R. González-Conejero ◽  
J. Rivera ◽  
F. Ortuño ◽  
P. Aparicio ◽  
...  

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.


2010 ◽  
Vol 30 (03) ◽  
pp. 150-155 ◽  
Author(s):  
J. W. Wang ◽  
J. Eikenboom

SummaryVon Willebrand factor (VWF) is a pivotal haemostatic protein mediating platelet adhesion to injured endothelium and carrying coagulation factor VIII (FVIII) in the circulation to protect it from premature clearance. Apart from the roles in haemostasis, VWF drives the formation of the endothelial cell specific Weibel-Palade bodies (WPBs), which serve as a regulated storage of VWF and other thrombotic and inflammatory factors. Defects in VWF could lead to the bleeding disorder von Willebrand disease (VWD).Extensive studies have shown that several mutations identified in VWD patients cause an intracellular retention of VWF. However, the effects of such mutations on the formation and function of its storage organelle are largely unknown. This review gives an overview on the role of VWF in WPB biogenesis and summarizes the limited data on the WPBs formed by VWD-causing mutant VWF.


Author(s):  
Abdulhafez A. Selim ◽  
Samir M. Abdelmagid ◽  
Reem A. Kanaan ◽  
Steven L. Smock ◽  
Thomas A. Owen ◽  
...  

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